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Human Blood and Mucosal Regulatory T Cells Express Activation Markers and Inhibitory Receptors in Inflammatory Bowel Disease.

Lord JD, Shows DM, Chen J, Thirlby RC - PLoS ONE (2015)

Bottom Line: In all samples, a similar fraction of FOXP3+ cells expressed the "natural" Treg (nTreg) marker Helios, suggesting that, in IBD, these cells are not entirely "induced" Tregs (iTregs) derived from activated effector T cells.Greater expression of activation markers was also seen in both Helios+ and Helios- Tregs, relative to FOXP3- cells, in both IBD patients and controls, indicating that Tregs are effectively activated by antigen in IBD.Extensive immunophenotyping revealed that Helios+ and Helios- mucosal Tregs exist at a similar frequency, and have a similar expression of inhibitory molecules and activation markers in patients with IBD as in healthy controls.

View Article: PubMed Central - PubMed

Affiliation: Translational Research Program at the Benaroya Research Institute at Virginia Mason, Seattle Washington, United States of America.

ABSTRACT

Background: FOXP3+ regulatory T cells (Tregs) are critical for preventing intestinal inflammation. However, FOXP3+ T cells are paradoxically increased in the intestines of patients with the inflammatory bowel disease (IBD) ulcerative colitis (UC) or Crohn's disease (CD). We determined whether these FOXP3+ cells in IBD patients share or lack the phenotype of such cells from patients without IBD.

Methods: We quantified and characterized FOXP3+ Treg populations, as well as FOXP3- CD4+ T cells, in the lamina propria lymphocytes (LPL) of intestine surgically resected from patients with and without IBD, and in the blood of controls or Crohn's patients with or without disease activity.

Results: In all samples, a similar fraction of FOXP3+ cells expressed the "natural" Treg (nTreg) marker Helios, suggesting that, in IBD, these cells are not entirely "induced" Tregs (iTregs) derived from activated effector T cells. Helios+ and Helios- FOXP3+ T cells demonstrated similar expression of maturation markers, activation markers, and inhibitory molecules between IBD patients and controls, while FOXP3- cells paradoxically expressed more of the inhibitory receptors CD39, CTLA4, and PD-1 in inflamed mucosa. Greater expression of activation markers was also seen in both Helios+ and Helios- Tregs, relative to FOXP3- cells, in both IBD patients and controls, indicating that Tregs are effectively activated by antigen in IBD.

Conclusions: Extensive immunophenotyping revealed that Helios+ and Helios- mucosal Tregs exist at a similar frequency, and have a similar expression of inhibitory molecules and activation markers in patients with IBD as in healthy controls.

No MeSH data available.


Related in: MedlinePlus

Tregs express inhibitory molecules in IBD no less than in controls.The percent of CD3+, CD4+ LPL (upper panels) or PBMC (lower panels) expressing CD25 (a), CD39 (b), CTLA4 (c), PD-1 (d), or TIGIT (e) is shown for non-IBD colon (black circles), the uninflamed (gray squares) or inflamed (gray triangles) colon from IBD patients (11 UC, 5 Crohn’s), or for blood from Crohn’s patients with (open gray triangles) or without (open gray squares) active symptoms (diarrhea, pain, and or bleeding), or from age/gender-matched healthy control subjects (gray circles). Positivity is relative to an isotype-matched control antibody for each marker.
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pone.0136485.g004: Tregs express inhibitory molecules in IBD no less than in controls.The percent of CD3+, CD4+ LPL (upper panels) or PBMC (lower panels) expressing CD25 (a), CD39 (b), CTLA4 (c), PD-1 (d), or TIGIT (e) is shown for non-IBD colon (black circles), the uninflamed (gray squares) or inflamed (gray triangles) colon from IBD patients (11 UC, 5 Crohn’s), or for blood from Crohn’s patients with (open gray triangles) or without (open gray squares) active symptoms (diarrhea, pain, and or bleeding), or from age/gender-matched healthy control subjects (gray circles). Positivity is relative to an isotype-matched control antibody for each marker.

Mentions: Although Tregs isolated from the LPL of IBD patients have been shown to have in vitro suppressive activity, some controversy exists as to whether in vitro assays of Treg-mediated inhibition accurately reflect their in vivo inhibitory activity. Therefore, we instead specifically evaluated the expression of a number of cell-surface receptors which have been associated with Treg inhibitory function, including CD25 (IL-2Rα), CD39 (ENTPD1), CD152 (CTLA4), CD279 (PD-1) and TIGIT (WUCAM, Vstm3) (Fig 4).


Human Blood and Mucosal Regulatory T Cells Express Activation Markers and Inhibitory Receptors in Inflammatory Bowel Disease.

Lord JD, Shows DM, Chen J, Thirlby RC - PLoS ONE (2015)

Tregs express inhibitory molecules in IBD no less than in controls.The percent of CD3+, CD4+ LPL (upper panels) or PBMC (lower panels) expressing CD25 (a), CD39 (b), CTLA4 (c), PD-1 (d), or TIGIT (e) is shown for non-IBD colon (black circles), the uninflamed (gray squares) or inflamed (gray triangles) colon from IBD patients (11 UC, 5 Crohn’s), or for blood from Crohn’s patients with (open gray triangles) or without (open gray squares) active symptoms (diarrhea, pain, and or bleeding), or from age/gender-matched healthy control subjects (gray circles). Positivity is relative to an isotype-matched control antibody for each marker.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4548948&req=5

pone.0136485.g004: Tregs express inhibitory molecules in IBD no less than in controls.The percent of CD3+, CD4+ LPL (upper panels) or PBMC (lower panels) expressing CD25 (a), CD39 (b), CTLA4 (c), PD-1 (d), or TIGIT (e) is shown for non-IBD colon (black circles), the uninflamed (gray squares) or inflamed (gray triangles) colon from IBD patients (11 UC, 5 Crohn’s), or for blood from Crohn’s patients with (open gray triangles) or without (open gray squares) active symptoms (diarrhea, pain, and or bleeding), or from age/gender-matched healthy control subjects (gray circles). Positivity is relative to an isotype-matched control antibody for each marker.
Mentions: Although Tregs isolated from the LPL of IBD patients have been shown to have in vitro suppressive activity, some controversy exists as to whether in vitro assays of Treg-mediated inhibition accurately reflect their in vivo inhibitory activity. Therefore, we instead specifically evaluated the expression of a number of cell-surface receptors which have been associated with Treg inhibitory function, including CD25 (IL-2Rα), CD39 (ENTPD1), CD152 (CTLA4), CD279 (PD-1) and TIGIT (WUCAM, Vstm3) (Fig 4).

Bottom Line: In all samples, a similar fraction of FOXP3+ cells expressed the "natural" Treg (nTreg) marker Helios, suggesting that, in IBD, these cells are not entirely "induced" Tregs (iTregs) derived from activated effector T cells.Greater expression of activation markers was also seen in both Helios+ and Helios- Tregs, relative to FOXP3- cells, in both IBD patients and controls, indicating that Tregs are effectively activated by antigen in IBD.Extensive immunophenotyping revealed that Helios+ and Helios- mucosal Tregs exist at a similar frequency, and have a similar expression of inhibitory molecules and activation markers in patients with IBD as in healthy controls.

View Article: PubMed Central - PubMed

Affiliation: Translational Research Program at the Benaroya Research Institute at Virginia Mason, Seattle Washington, United States of America.

ABSTRACT

Background: FOXP3+ regulatory T cells (Tregs) are critical for preventing intestinal inflammation. However, FOXP3+ T cells are paradoxically increased in the intestines of patients with the inflammatory bowel disease (IBD) ulcerative colitis (UC) or Crohn's disease (CD). We determined whether these FOXP3+ cells in IBD patients share or lack the phenotype of such cells from patients without IBD.

Methods: We quantified and characterized FOXP3+ Treg populations, as well as FOXP3- CD4+ T cells, in the lamina propria lymphocytes (LPL) of intestine surgically resected from patients with and without IBD, and in the blood of controls or Crohn's patients with or without disease activity.

Results: In all samples, a similar fraction of FOXP3+ cells expressed the "natural" Treg (nTreg) marker Helios, suggesting that, in IBD, these cells are not entirely "induced" Tregs (iTregs) derived from activated effector T cells. Helios+ and Helios- FOXP3+ T cells demonstrated similar expression of maturation markers, activation markers, and inhibitory molecules between IBD patients and controls, while FOXP3- cells paradoxically expressed more of the inhibitory receptors CD39, CTLA4, and PD-1 in inflamed mucosa. Greater expression of activation markers was also seen in both Helios+ and Helios- Tregs, relative to FOXP3- cells, in both IBD patients and controls, indicating that Tregs are effectively activated by antigen in IBD.

Conclusions: Extensive immunophenotyping revealed that Helios+ and Helios- mucosal Tregs exist at a similar frequency, and have a similar expression of inhibitory molecules and activation markers in patients with IBD as in healthy controls.

No MeSH data available.


Related in: MedlinePlus